Hormone-sensitive lipase (HSL) catalyses the rate-limiting step in adipocyte lipolysis. Short-term hormonal regulation of HSL activity is well characterized, whereas little is known about the control of HSL gene expression. We have measured HSL mRNA content of 3T3-F442A and BFC-1 adipocytes in response to the cAMP analogue 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP) and to the phorbol ester phorbol 12-myristate 13-acetate (PMA) by Northern blot, using a specific mouse cDNA fragment. Treatment of the cells for 12 or 6 h with, respectively, 0.5 mM 8-CPT-cAMP or 1 µM PMA produced a maximal decrease of about 60% in HSL mRNA. These effects were unaffected by the protein-synthesis inhibitor anisomycin, suggesting that cAMP and PMA actions were direct. The reduction in HSL mRNA was accompanied by a reduction in HSL total activity. The intracellular routes that cAMP and PMA follow for inducing such an effect seemed clearly independent. (i) After desensitization of the protein kinase C regulation pathway by a 24 h treatment of the cells with 1 µM PMA, PMA action was abolished whereas cAMP was still fully active. (ii) Treatment with saturating concentrations of both agents produced an additive effect. (iii) The synthetic glucocorticoid dexamethasone had no proper effect on HSL gene expression but potentiated cAMP action without affecting PMA action. cAMP inhibitory action on HSL is unexpected. Indeed, the second messenger of catecholamines is the main activator of HSL by phosphorylation. We envision that a long-term cAMP treatment of adipocytes induces a counter-regulatory process that reduces HSL content and, ultimately, limits fatty acid depletion from stored triacylglycerols.
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September 1996
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Research Article|
September 15 1996
Inhibition of hormone-sensitive lipase gene expression by cAMP and phorbol esters in 3T3-F442A and BFC-1 adipocytes
Emmanuelle PLÉE-GAUTIER;
Emmanuelle PLÉE-GAUTIER
*Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, C.N.R.S., 9 rue Jules Hetzel, 92190 Meudon, France
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Jacques GROBER;
Jacques GROBER
†INSERM Unité 317, Institut Louis Bugnard, Bâtiment L3, Faculté de Médecine, Hôpital Rangueil, F-31054 Toulouse Cedex, France
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Eric DUPLUS;
Eric DUPLUS
*Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, C.N.R.S., 9 rue Jules Hetzel, 92190 Meudon, France
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Dominique LANGIN;
Dominique LANGIN
†INSERM Unité 317, Institut Louis Bugnard, Bâtiment L3, Faculté de Médecine, Hôpital Rangueil, F-31054 Toulouse Cedex, France
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Claude FOREST
Claude FOREST
‡
*Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, C.N.R.S., 9 rue Jules Hetzel, 92190 Meudon, France
‡To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
March 04 1996
Revision Received:
April 22 1996
Accepted:
May 10 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 318 (3): 1057–1063.
Article history
Received:
March 04 1996
Revision Received:
April 22 1996
Accepted:
May 10 1996
Citation
Emmanuelle PLÉE-GAUTIER, Jacques GROBER, Eric DUPLUS, Dominique LANGIN, Claude FOREST; Inhibition of hormone-sensitive lipase gene expression by cAMP and phorbol esters in 3T3-F442A and BFC-1 adipocytes. Biochem J 15 September 1996; 318 (3): 1057–1063. doi: https://doi.org/10.1042/bj3181057
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